The U.S. has set a goal to end the HIV epidemic by the year 2030, which can be achieved but only if targeted approaches are implemented with at-risk populations to address known barriers of engagement along the HIV prevention and care continua. Populations of greatest concern include young men who have sex with men (YMSM), especially YMSM of color, who now account for the vast majority of new HIV infections each year. Transgender and gender non-conforming/non-binary youth are also at high risk for HIV acquisition, accounting for an increasing proportion of new infections each year. In 2015, we were awarded a grant from NIDA to establish a new cohort of 448 African American/Black (AA/B) and Latino YMSM, called the Healthy Young Men?s (HYM) Cohort. We also received an administrative supplement to collect two waves of data from a smaller cohort of B/AA and Latinx 108 transgender and gender nonconforming/non-binary youth (TGMY), called the TRUTH Cohort. Both HYM and TRUTH participants were 16 to 24 years of age at the time of recruitment. The overarching aim was to conduct longitudinal research focused on these youths? engagement in the HIV prevention and care continua in an effort to prevent new HIV infections, reduce transmission, and reduce HIV/AIDS-related disparities. Mixed methods research is conducted using qualitative interviews, a self- report survey, drug screening, and testing for sexually transmitted infections (STIs) and HIV. Biospecimens (plasma, buffy coat, rectal swabs) are also collected and banked. Analyses performed to date provide clear evidence that participants in both cohorts are at high risk for HIV, drug use, and mental health/psychiatric conditions. Intersectional stigma?i.e., experiences of stigma stemming from multiple, intersecting identities1- 5?also appears to discourage AA/B and Latinx YMSM and TGMY from engaging in care and perhaps may impact their developmental arcs of risk, transmission, and health. Building on this work, we are proposing to longitudinally: i) examine B/L-YMSM?s engagement in the HIV prevention and care continua, as well as their developmental transitions and trajectories in drug use, STI/HIV infection, health, and psychiatric/mental health comorbidities (Aim 1); ii) examine TGMY?s engagement in the HIV prevention and care continua and identify shared and unique transitions and trajectories with respect to TGMY?s use of drugs, infections with STI/HIV, health and psychiatric/mental health comorbidities (Aim 2); and iii) serve as a local and national resource for collaborations and dissemination. We will actively participate in and contribute to the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO), the Coordinating Center for NIDA?s U01 cohorts. We will also partner with key stakeholders (e.g., community organizations, policy makers) and collaborate with trainees, early career faculty and investigators across the translational spectrum (Aim 3).